Elucidation of the physicochemical and functional characteristics of proteins of the complement system has made it possible in the past decade to undertake more sophisticated studies of complement biosynthesis. The methods developed in the course of these studies have been applied to investigations of the molecular mechanisms that account for genetic and acquired diseases of the complement system. The availability of this information might permit the rational design of therapeutic approaches to these and perhaps other more common protein deficiency states. Accordingly in the proposed project, several lines of experimental investigations will be undertaken. These include cell free synthesis system, hybridization of somatic cells in vitro and detailed studies of the effects of pharmacologic and biologic factors on cell physiology.